The University of Minnesota is one of the original 14 US TrialNet centers. We have implemented 8 protocols to date. Our particular strength has been enrollment in prevention and intervention trials, where we are the number 1 overall recruiter. Our recruitment in the Natural History Study (NHS), however, has been average. In order to improve this, we have embarked on a new collaboration with Dr. Kevin Peterson, Director of Research for the UM Department of Family Medicine and Community Health and Director of the Minnesota Academy of Family Physicians Research Network. We anticipate access immediately to more than 1000 patients with T1D, with increased future access as this network grows. In this application we are proposing therapy with autologous Tregulatory cells (Tregs). Previous protocols have attempted to increase endogenous Treg numbers with drugs. Tregs themselves have not previously been available in sufficient numbers for clinical use. Our group is the first to develop a clinically applicable selection and culture method for manufacturing large numbers of Tregs from peripheral blood. Preliminary data in animal models and in humans with leukemia suggest that this product is safe. This is a single site, single arm phase 1 dose escalation trial. Adult subjects with recent (3-12 months) onset T1D and persistent C-peptide secretion will receive an infusion of autologous peripheral blood- derived Tregs (CD4+/CD25+/FoxP3+) using new methodology developed at the UM Molecular and Cellular Therapeutics cGMP Facility. Cells will be collected by leukapheresis and expanded in culture for up to 35 days and then cryopreserved. Immediately following leukapheresis, subjects will receive a course of thymoglobulin, 4 doses over 1 week. Thawed, autologous Tregs will be infused approximately 2 months later, at a time when there is no residual detectable rabbit antibody in the circulation. Safety and immunologic data and C-peptide secretion will be followed for 2 years. The long-term goal is to gather preliminary data in anticipation of an intervention trial of peripheral-blood derived autologous CD4+/CD25+/FoxP3+ treatment of new onset T1D.